TY - JOUR
T1 - Toll-like receptors in tumor immunotherapy
AU - Paulos, Chrystal M.
AU - Kaiser, Andrew
AU - Wrzesinski, Claudia
AU - Hinrichs, Christian S.
AU - Cassard, Lydie
AU - Boni, Andrea
AU - Muranski, Pawel
AU - Sanchez-Perez, Luis
AU - Palmer, Douglas C.
AU - Yu, Zhiya
AU - Antony, Paul A.
AU - Gattinoni, Luca
AU - Rosenberg, Steven A.
AU - Restifo, Nicholas P.
PY - 2007/9/15
Y1 - 2007/9/15
N2 - Lymphodepletion with chemotherapeutic agents or total body irradiation (TBI) before adoptive transfer of tumor-specific T cells is a critical advancement in the treatment of patients with melanoma. More than 50% of patients that are refractory to other treatments experience an objective or curative response with this approach. Emerging data indicate that the key mechanisms underlying how TBI augments the functions of adoptively transferred T cells include (a) the depletion of regulatory T cells (Treg) and myeloid-derived suppressor cells that limit the function and proliferation of adoptively transferred cells; (b) the removal of immune cells that act as "sinks" for homeostatic cytokines, whose levels increase after lymphodepletion; and (c) the activation of the innate immune system via Toll-like receptor 4 signaling, which is engaged by microbial lipopolysaccharide that translocated across the radiation-injured gut. Here, we review these mechanisms and focus on the effect of Toll-like receptor agonists in adoptive immunotherapy. We also discuss alternate regimens to chemotherapy or TBI, which might be used to safely treat patients with advanced disease and promote tumor regression.
AB - Lymphodepletion with chemotherapeutic agents or total body irradiation (TBI) before adoptive transfer of tumor-specific T cells is a critical advancement in the treatment of patients with melanoma. More than 50% of patients that are refractory to other treatments experience an objective or curative response with this approach. Emerging data indicate that the key mechanisms underlying how TBI augments the functions of adoptively transferred T cells include (a) the depletion of regulatory T cells (Treg) and myeloid-derived suppressor cells that limit the function and proliferation of adoptively transferred cells; (b) the removal of immune cells that act as "sinks" for homeostatic cytokines, whose levels increase after lymphodepletion; and (c) the activation of the innate immune system via Toll-like receptor 4 signaling, which is engaged by microbial lipopolysaccharide that translocated across the radiation-injured gut. Here, we review these mechanisms and focus on the effect of Toll-like receptor agonists in adoptive immunotherapy. We also discuss alternate regimens to chemotherapy or TBI, which might be used to safely treat patients with advanced disease and promote tumor regression.
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U2 - 10.1158/1078-0432.CCR-07-1378
DO - 10.1158/1078-0432.CCR-07-1378
M3 - Review article
C2 - 17875756
AN - SCOPUS:34848903051
SN - 1078-0432
VL - 13
SP - 5280
EP - 5289
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 18
ER -